1. Field of the Invention
The present invention relates, in general, to a method of obtaining policosanols from novel sources, and to compositions obtained by such method. The present invention also relate to a method of reducing cholesterol level in humans and animals. The present invention further relates to a composition comprising policosanols, with or without additional additives, in concentrations effective for cholesterol reduction.
2. Related Art
Currently, approximately 20% of the U.S. population has hyperlipidemia or elevated levels of serum cholesterol, which have been implicated as a leading cause of heart disease. More recently, in an effort to understand and alleviate the impact of coronary heart disease (CHD) on the modem world, the lipid profile has been examined more closely. A total cholesterol level is an obvious risk factor; however, a high level of the bulky low-density lipoproteins (LDL) in the blood stream is also cause for concern. These bulky macro proteins can easily get stuck in the intricate cardiovascular system, which leads to further blockage. Furthermore, a low level of the “cleaner” lipoproteins can be harmful as well. High-density lipoproteins (HDL) are compact, heavy macro proteins that move through the system with more precision and actually have beneficial effects as they sweep through arteries and knock loose stuck materials along the way.
Traditional strategies to reduce blood cholesterol levels have typically been to reduce or eliminate dietary intake of cholesterol. However, the normal diet of most western civilized individuals does not comply with these strategies. The health care profession has since put much emphasis on pharmaceutical tools to assist in lowering cholesterol. These statin drugs, or antihypercholesterolemic drugs, such as Lovastatin™, have proven effective; however, there is room for improvement. Statins are effective for only 50% of the people taking them and they cause side effects such as liver disease and muscle weakness.
Plant-derived long chain fatty or waxy alcohols (generically referred to herein as policosanols) have been demonstrated as having biological activity including lipid effects as well as ergogenic effects with benefits in cardiovascular, cerebral and muscular systems. Also, these compounds have activity as growth regulators for plants. 1-Triacontanol, or myricyl alcohol has been demonstrated as being a growth stimulant on a wide range of plants (U.S. Pat. No. 4,150,970). Recently, such compounds have been associated with inhibiting cholesterol biosynthesis and increasing LDL receptor-dependent processing (Menéendez, et al., Biol. Res. 27:199 (1994); Brit. J. Nutrition, 77:923 (1997)) with such effects being demonstrated in patients with type II hypercholesterolemia and dyslipidemia associated with non-insulin dependent diabetes mellitus (Mirkin, et al., Int. J. Clin. Pharm. Res. 21:31–41 (2001). Other applications that have been reported in the literature include platelet hyperaggregability, ischemia and thrombosis, prevention of drug-induced gastric ulcer and improvement of male sexual activity (WO 94/07830).
Free primary alcohols are found in many plant waxes; e.g., in leaf bark and stem waxes of most plants. Natural plant waxes may be grouped into waxes of palms, grasses and sedges, broad-leaf trees, and narrow-leaf trees (Albin H. Warth in The Chemistry and Technology of Waxes, 1956, Reinhold Publishing Corporation, NY. Pp. 76–341). The sugar cane, Saccharum officinarum L., of the grass family, order Graminenae, has an appreciable deposit of wax on the surface of the stalks. This wax is of considerable economic value as it is rich in long chain fatty alcohols.
Numerous patents and patent applications describe methods for the isolation and purification of long chain fatty alcohols (see, for example, JP 60-119514; JP 62-87537, U.S. Pat. No. 5,856,316 and WO 94/07830). Waxes from plant sources have been fractionated into different classes such as hydrocarbons, second alcohols, esters, ketones, aldehydes, free alcohols and acids. Usually, long chain free alcohols in plants are present either as free alcohols or as esters of these alcohols with acids. Such esters usually contain an even number of carbon atoms in the range C20–C54. The long chain free alcohols usually found are straight chain primary alcohols and mainly of an even length (C20–C36). Sugar cane wax, for example, may contain up to 26% free and esterified long chain alcohols while Carnauba wax may contain up to 52.5% free and esterified long chain alcohols (Hamilton, et al. Plant waxes in Topics in Lipid Chemistry, 3:199–269 (1972), F. D. Gunstone (ed.), John Wiley and Sons, Inc., NY).
It is well known in the literature that long chain aliphatic wax alcohols, referred to as policosanols, have anti-cholesterol effects. Gouni-Berthold et al. shows that doses of 10 to 20 mg per day of policosanol lowers total cholesterol (Gouni-Berthold, I. et al., Am. Heart J, 143:356–65 (2002)). U.S. Pat. No. 5,952,393 and U.S. Application No. 20010034338A1 disclose a purportedly synergistic anti-cholesterol effect of a composition comprising phytosterols and policosanols. U.S. Pat. No. 6,197,832 discloses the method of administering this composition of phytosterols and policosanols.
European Patent Application EP1 108 365 A2 discloses encapsulated policosanols for use in food applications.
U.S. Pat. No. 3,031,376 discloses the pharmaceutical use of certain long chain fatty alcohols in a method of increasing oxygen utilization.
European Patent Application EP1 108 363 A1 discloses processes for incorporation of long chain alcohols in edible oils.
European Patent Application EP1 108 364 A2 discloses a method for admixture of long chain alcohols in sterol compounds.
U.S. Pat. No. 6,277,403 discloses fat continuous emulsions containing, among other components, long chain alcohols having at least 20 carbon atoms in the alcohol chain.
U.S. Pat. No. 4,981,699 discloses a method for preparing an edible composition by extracting alcohols of 24–34 carbon atoms at subcritical or supercritical conditions and admixing peptides therewith.
U.S. Patent Application No. 2002/0016314A1 discloses compositions for reducing blood cholesterol and triglycerides comprising policosanol esters.
U.S. Pat. Nos. 5,865,316 and 5,663,156, and PCT Publication No. WO94/07830 disclose an extraction method of policosanols out of sugar cane wax and uses of those policosanol mixtures as a treatment for high cholesterol.
U.S. Pat. No. 6,328,998 discloses a method of treating high cholesterol with a pharmaceutically acceptable salt of L-carnitine and hexacosanol.
There are numerous other reports in the art for extraction of long chain alcohols from plant sources. For example, Staby and De Hertogh (Hortscience 74:411–412 (1972)) describe a process for separation of octacosanol in extracts from “Wedgwood” iris shots; Joshi and Singh report on the extraction of octosanol from Gmelina arborea (Heartwoods) (Z. Naturforsch, 25:693–694 (1970)); Piatak and Reimann describe isolation of octosanol from Euphorbia Corollata (Phytochemistry, 9:2585–2586 (1970)). Other sources of free primary alcohols in oils and waxes have included germs, kernels and other components of nuts, seeds, fruits and cereals (Kawanishi, et al., JAOCS 68:869–872 (1991)).
Methods in the art have been described for the purification of long chain free alcohols. These include crystallization, chromatographic separation (Hamiton, et al., Plant waxes in Topics in Lipid Chemistry, 3:199–269 (1972), F. D. Gunstone (ed.), John Wiley and Sons, Inc., NY.), gel permeation chromatography (WO 99/48853); multiple crystallization in different solvents (U.S. Pat. No. 6,225,354; EP 0654262).
Policosanols have been tested directly against statin drugs and they show similar or better total cholesterol reduction while policosanols improved HDL values, as well (Clinical reviews of Dalmer Laboratories).
Addition of policosanols or policosanols combined with other additives to foods will give the consumer who is concerned about lowering their cholesterol easier choices and more palatable options. For example, in 1999, the FDA approved a health claim of soy protein to reduce the risk of coronary heart disease. Studies showed that 25 grams of soy protein (or more) added to a daily diet had a cholesterol lowering effect. However, it has been noted that it is hard for the average consumer to consume 25 grams of soy protein. One object of the present invention would be to add policosanols to food already containing soy protein. The anticholesterol effect of the policosanols combined with the same effects of soy protein would be additive and the consumer would therefore have to consume less soy protein a day to reduce their risk of coronary heart disease. Also, since it is not known specifically how soy protein reduces cholesterol, there is a possibility policosanols and the soy protein would not only have an additive effect, but a synergistic effect as well.